The reactions of peroxy radicals with 2,4,6-tri-t-butyl substituted phenol, aniline, and thiophenol have been examined by a kinetic method. The primary process involves abstraction of the hydrogen atom attached to the functional group, since all three compounds show fairly large isotope effects when this hydrogen is replaced by deuterium. The phenol and aniline react with about two peroxy radicals per molecule. In contrast, the thiophenol reacts with only a single peroxy radical. ,

The substituted benzamides are used clinically both as antipsychotics and as stimulants of gastric motility. The antipsychotic effects are considered to be a consequence of their central dopamine antagonist properties, but there is evidence that the gastric stimulatory effects may be mediated by other mechanisms. Clebopride (3) is a substituted benzamide that although marketed for its stimulatory effects on gastric motility, is also a potent central dopamine antagonist. The corresponding anilide, BRL 20596 (4a), where the amide bond has been reversed, has been synthesized and found to lack gastric stimulatory activity. However, the potent central dopamine antagonist activity is retained, suggesting that benzamides and anilides have similar affinities for central dopamine receptors. The implications of the conformations adopted by benzamides and anilides at such receptors are discussed. Evidence is also presented that there is a further lipophilic binding site on such receptors for which the N-benzyl group is an optimal fit.

3-Chloro-and 3-bromomethacrylonitrile (E-and Z-) have been shown to undergo nucleophilic substitution at C-3 with > 9 5 % retention of configuration. The configuration of each product has been established by the use of nuclear magnetic resonance spectroscopy. The thermodynamic position of equilibrium for each pair of E-Z isomers has been determined and the factors which affect this equilibrium are discussed. Some form of cis interactions, non-steric in origin, dominates in determining the equilibrium positions.

Following the discovery that 3-(dimethylamino)-1,1-diphenyl-2-propanol hydrobromide (1) possesses potent reserpine-prevention activity in mice, a series of analogues of 1 was synthesized and evaluated as potential antidepressant agents. Several routes to analogues of 1 were evaluated, the most generally applicable of which was the regiospecific ring opening of a suitably functionalized 1,1-diaryl-2,3-epoxypropane (obtained in three stages from the corresponding benzophenone) with the appropriate amine. The more interesting compounds of the series were evaluated for their propensity to cause undesirable peripheral anticholinergic effects, all compounds tested being markedly less active than imipramine on this parameter. On the basis of its good activity in biochemical and pharmacological animal models of depression, together with its relative lack of anticholinergic side effects, 1-(3-chlorophenyl)-3-(dimethylamino)-1-phenyl-2-propanol hydrochloride (20, BRL 14342) was chosen for further evaluation.

Baeyer-Villiger oxidation of 2-acetylbiphenylene and its 6-benzoyl and 3-methoxy-derivatives gave the corresponding 2-acetoxy-compounds. Similar oxidation of 2,6-diacetylbiphenylene gave a mixture of 2-acetoxy-6-acetyl-and 2,6-diacetoxy-biphenylene. These compounds were converted into 2-acetyl-6-methoxy-and 2.6-dimethoxy-biphenylene, respectively, by combined hydrolysis and methylation. Oxidation of 2,7-diacetylbiphenylene gave the 2.7-diacetoxy-compound.Fries rearrangement of 2-acetoxybiphenylene gave the 2-acetyl-3-hydroxy-compound, which was methylated to 2-acetyl-3-methoxybiphenylene. The latter was also obtained by Friedel-Crafts acetylation of 2-methoxybiphenylene.RECENTLY it was reported2 that 2-benzoyl-but not 2-acetyl-biphenylene could be oxidised by peracetic acid in acetic acid (Baeyer-Villiger reaction3) to give the corresponding ester of 2-hydroxybiphenylene. This oxidation required a relatively large amount of concentrated sulphuric acid as catalyst. It has now been found that 2-acetyl-can be oxidised to 2-acetoxybiphenylene in 84% yield in the absence of added sulphuric acid provided that stronger peracetic acid is used (commercial peracetic acid often contains traces of sulphuric acid which must be removed, otherwise the yield is decreased to 61%).2-Acetyl-6-benzoylbiphenylene (I ; R = PhCO) (m. p.175") has been made by acetylation of 2-benzoylbiphenylene and, in lower yield, by benzoylation of 2-acetylbiphenylene. When it was treated with peracetic acid the more reactive carbonyl group, i.e., the acetyl group, underwent preferential oxidation to give a mixture of 2-acetoxy-6-benzoyl-and 2-acetoxy-6benzoyloxy-biphenylene, which was very difficult to separate. These two products, on combined hydrolysis and methylation, gave 2-benzoyl-6-methoxy-and 2,6-dimethoxy-biphenylene, respectively. The formation of the latter confirmed the orientation assigned to 2-acetyl-6-benzoylbiphenylene.2,6-Diacetylbiphenylene (I ; R = CH,CO) (m. p. 254.) is sparingly soluble in peracetic acid, but it reacted slowly to give a mixture of 2,6-diacetoxy-and a little 2-acetoxy-6-acetyl-biphenylene. These compounds were converted into 2,6-dime thoxybiphenylene and 2-acetyl-6-methoxybiphenylene ( I ; R = MeO), respectively, by hydrolysis and methylation. 2,7-Diacetylbiphenylene (m. p. 174") is moderately soluble in acetic acid and oxidation with peracetic acid readily occurred, though the yield of 2,7-diacetoxybiphenylene was rather low (23%).2-Acetoxy-biphenylene readily underwent Fries migration to give 2-acetyl-3-hydroxybiphenylene , which on